The Role of the Deubiquitylase MYSM1 During Alphavirus Infection Amer Nubgan The members of the genus Alphavirus are positive-sense RNA viruses and it is one of two within the family Togaviridae. Most alphaviruses are predominantly transmitted to susceptible vertebrates by a mosquito vector. Alphavirus disease in humans can be severely debilitating, and depending on the particular viral species, infection may result in encephalitis and possibly life threatening symptoms. Chikungunya virus (CHIKV) is the aetiological agent represents a substantial health burden to affected populations, with clinical symptoms that include severe joint and muscle pain, rashes, and fever, as well as prolonged periods of disability in some patients. In recent years, CHIKV has received significant attention from public health authorities as a consequence of the dramatic emergence infections in the Indian Ocean islands and the Caribbean as well as the recent emergence of CHIKV in the Americas. Infections have also been reported around Europe such as in Italy, France and Greece. Currently, no safe, approved or effective vaccine or treatment exists for CHIKV infection. The ubiquitin-proteasome system (UPS), the major intracellular proteolytic pathway, mediates different kinds of cellular processes, which may be targeted by viruses to aid their replication within cells. In recent years it has been well established that both the forward reaction of ubiquitination, and the reverse reaction of deubiquitination are targeted during virus infection to enhance their replication, either by targeting of cellular proteins or encoding viral homologues of key pathway proteins. The reverse reaction is undertaken by a large family of enzymes termed deubiquitylases or DUBs, and many of these have been shown to play a crucial role, not only in virus replication but also in the regulation of the immune system and vesicle trafficking. The DUBs are attractive drug targets and have increasingly been implicated in cellular processes germane to malignancy which makes the continued characterisation of the role of DUBs during virus infection a worthwhile objective. In on-going experiments in the research group a DUB siRNA pools library screen identified 12 DUBs (USP1, USP4, USP5, USP34, USP45, USP46, OTUD6A, UCHL1, JOSD2, BRCC3 and MYSM1). Depletion of these hits in HeLa cells lead to an increase in cell viability following Semiliki Forest Virus (SFV) infection (and predicted to be pro-viral) and thus could potential be candidate antiviral targets. Inroads into understanding the role of the DUB hits during the alphavirus infection, focusing initial on the BSL2 model virus SFV, and extending this to CHIKV (at BSL3). In the present study, further screening focused on the deconvolution siRNA pools for the DUB hits. Investigation of the subsequent follow up experiments with one strong candidate DUB from this list, MYSM1. Two different approaches were taken. Firstly, the effect of depletion of MYSM1 by siRNA treatment was further investigated in HeLa cells. Secondly, the analysis was extended to investigate the role of MYSM1 in fibroblasts utilising MYSM1 genetic knockout murine embryo fibroblasts. Results from this study indicate that depletion of MYSM1 in HeLa cells by siRNAs resulted in a reduction in both SFV and CHIKV replication, as assayed by measuring RNA levels and plaque formation. It was also found that MYSM1 genetic knockout in MEF cells lead to increase in both SFV and CHIKV replication. In addition, depletion of MYSM1 by siRNAs in MRC-5 cells lead to increase in SFV replication. In conclusion, MYSM1 generated interesting data, implying a role during virus infection that appeared to depend on the cell type being infected. Up to now it is unclear what the effector mechanisms are that contribute to these observations, subject to further mechanistic and functional studies, may increase the options available for targeting this vital DUB during Alphavirus infections.
Klebsiella pneumoniae has been found in the urinary tract of some bladder cancer patients. Bacterial presence within tumor tissue may affect the tumor-microenvironment and consequently influence cancer behavior, development, and treatment response. This study investigated mesenchymal and stemness transdifferentiation of bladder cancer cell line due to environmental stress of K. pneumoniae. Cultures of urothelial bladder cancer cell line (T24) were infected with K. pneumoniae with different multiplicity of infection (MOI) for two and four days. Transdifferentiation-associated features were morphologically assessed.
Moreover, transdifferentiation markers were estimated using Q-PCR and immunohistoc
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Infection with Trichomonas vaginalis and its relation to some diseases have lately had much attention. The objective of this study was to assess the infection rate of T. vaginalis and its relation to pelvic inflammatory diseases, infertility, and vaginosis. The study also assessed some demographic, clinical, and immunological parameters in women infected with T. vaginalis. The study included 160 non-pregnant married women who attended some private clinics and public hospitals in Baghdad from October 2020 to February 2021. All participants had symptoms of vaginal discharge only or vaginal discharge with lower abdominal pain. The participants were divided into an infertility group (n = 61) and fertility group (n = 99). The participant
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إن موضوع الشرق الأوسط بشكل عام اتخذ أهمية كبيرة في الكتابات والمؤلفات التي صدرت منذ بداية النصف الأول من عقد التسعينات من القرن المنصرم مع بدايات مشاريع السلام التي أعقبت انهيار الاتحاد السوفيتي وتغير الخارطة السياسية والاقتصادية والايديولوجية للعالم .وعلى الرغم ان المصطلح ليس بجديد الا ان تعابير المصطلح وددلالاته تتغير مع تغير موازين القوى واتجاهات المصالح. إذ انتقل من مصطلح جغرافي الى
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The goal of current research to the definition of environmental awareness in the curriculum and its role in sustainable environmental planning, was the research community official regular educational schools (kindergarten, primary, secondary) for the province of Baghdad - Iraq, the sample consisted search of (100) teacher and a teacher, and what research was descriptive analytical, researchers have selected the right tool for the research procedures (closed) questionnaire, distributed to the research sample, has been used by researchers appropriate statistical methods for procedures including: the weighted average extraction unit paragraph,
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Abstract
The following research is marked by "social intelligence and its role in demonstration the potential abilities for individuals." The discussion dealt with the concepts of contemporary is very important because of their significant role in influencing the work of the Organization, as adopted link between the concepts of social intelligence and the potential role of the first to show the second .The research hypotheses tested in three health institutions in the city of Mosul, the research community is represented (Al-Salam Hospital and General Hospital and the son of ether), while the sample were the leaders of these institutio
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An essential tool for studying the web is its ability to show how energy moves through an ecosystem. Understanding and elucidating the relationship between species variety and their placement within the inclusive trophic dynamics is also beneficial. A food web ecological model with prey and two rival predators under fear and wind flow conditions is developed in this article. The boundedness and positivity of the system’s solution are established mathematically. The stability and existence constraints of the system’s equilibria are examined. The proposed system’s persistence limitations are established. Additionally, the bifurcation analysis of every potential equilibrium is examined using the Sotomayor theorem. To describe the
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Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide, with tumor angiogenesis playing a pivotal role in its progression and metastasis. CD144 (VE-cadherin), a calcium-dependent adhesion molecule, is critical for endothelial cell integrity and has been linked to tumor angiogenesis and cancer stem cell phenotypes. This study aimed to evaluate the immunohistochemical expression of CD144 in benign colorectal lesions, normal adjacent tumor tissue (NRAT), and tumor tissues to elucidate its role in colorectal cancer progression. Multiple techniques, including immunohistochemistry, flow cytometry, Western blot, and qPCR, were used to assess CD144 expression and its association with the VEGF/VEGFR2 signaling pat
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Consistent with developments emerging environmental and canaccept by Iraq of the opportunities and challenges ahead in many fields,including economic areas, it requires the face of those developments andadaptation by adopting a lot of related concepts, including the concept ofcorporate governance and commitment to its principles, standards andmechanisms, especially those related to the formation of audit committeesand identify the tasks and duties entrusted to its members and terms oftheir independence as well as the rehabilitation of both scientific andpractical manner that is consistent with the interests of shareholders andother stakeholders in the companies, including banks, research sample, theresearch aims to shed light on the conc
... Show MoreThis research focuses on detecting the financial corruption cases in Iraq in light of adoption the strategic audit, the paper deals with the problem of the proliferation corruption cases particularly financial in Iraq and dramatically in the presence of audit and control devices as well as inspection and integrity devices, which indicates the existence of deficiencies and weaknesses in those devices in the implementation of audit and control functions in order to detect the corruption cases in the economic units in Iraq.
Stems objective of this research through the provision of approach of strategic audit concepts and indicate the extent importance of adopting of strategic audit as a means to detect the f
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The article examines metaphors as one of the fundamental means used by D. Rubina when writing the novel “Parsley Syndrome” to form images of dolls as equal heroes of the work. The author of the article continues research related to the work of Dina Ilinichna Rubina, a representative of modern Russian prose.